Levetiracetam improves verbal memory in high-grade glioma patients

Abstract

Background: Treatment of high-grade glioma (HGG) patients with anti-epileptic drugs (AEDs) has met with various side effects, such as cognitive deterioration. The cognitive effects of both older and newer AEDs in HGG patients are largely unknown. The aim of this study was to determine the effect of older and newer AEDs on cognitive performance in postoperative HGG patients.

Methods: We selected HGG patients from 3 separate cohorts for use of older, newer, or no AEDs, as they represented distinct treatment eras and provided the opportunity to compare older and newer AEDs. In all 3 cohorts, patients were included within 6 weeks following neurosurgery before the start of postoperative treatment. Cognitive functioning was evaluated by an extensive neuropsychological assessment, executed in 6 cognitive domains (attention, executive functioning, verbal memory, working memory, psychomotor functioning, and information processing speed).

Results: One hundred seventeen patients met the inclusion criteria; 44 patients used no AED, 35 were on monotherapy with a newer AED (all levetiracetam), and 38 were on monotherapy with an older AED (valproic acid or phenytoin). Patients on older and newer AEDs performed equally well as patients not on an AED, and patients on levetiracetam performed even better on verbal memory tests than patients not on an AED. Post-hoc analyses revealed that within the group using older AEDs, patients on valproic acid performed better than patients on phenytoin.

Conclusions: Neither levetiracetam nor valproic acid was associated with additional cognitive deficits in HGG patients. Both AEDs even appeared to have a beneficial effect on verbal memory in these patients.

Fig. 1.

Flowchart of patient inclusion. Abbreviations: NPA, neuropsychological assessment; VPA, valproic acid; LEV, levetiracetam; PHT, phenytoin; CBZ, carbamazepine; poly, polytherapy.

Fig. 2.

Mean results of the visual verbal learning test in patients on levetiracetam and those not using AEDs. Abbreviation: LEV, levetiracetam. Error bars are SDs. **P < .01.

Fig. 3.

Mean cognitive domain z-scores of patients per AED used. Abbreviations: EF, executive functioning; VM, verbal memory; WM, working memory; IPS, information processing speed; A, attention; PS, psychomotor speed; Total, total cognitive functioning of 117 glioma patients using no AEDs (n = 44); LEV, levetiracetam (n = 35); VPA, valproic acid (n = 22) or PHT, phenytoin (n = 16).